Taste receptor type 2 member 4 and Taste receptor type 2 member 14 (TAS2R4/TAS2R14)

Taste receptor type 2 member 4 (TAS2R4) and Taste receptor type 2 member 14 (TAS2R14) are G protein-coupled receptors (GPCRs) that function as bitter taste sensors (UniProt, Wikipedia). Beyond their role in the oral cavity, these receptors are expressed in extraoral tissues, including airway smooth muscle, the gastrointestinal tract, and various immune and cancer cells (PMC, PubMed). TAS2R14 is notably promiscuous, recognizing a broad spectrum of chemically diverse ligands, including several clinical drugs such as flufenamic acid and chloroquine (Nature, PubMed). In the respiratory system, activation of TAS2R4 and TAS2R14 triggers signaling pathways that lead to the relaxation of airway smooth muscle, positioning them as potential therapeutic targets for asthma and chronic obstructive pulmonary disease (COPD) (PMC, PubMed). Furthermore, these receptors have been implicated in oncology, where their activation can inhibit the proliferation and migration of breast and prostate cancer cells (PMC). Recent structural insights, including the discovery of an intracellular binding pocket in TAS2R14, are facilitating the development of more potent and selective agonists for therapeutic use (Nature, PubMed). However, challenges remain regarding the potential for off-target effects and the inherent bitterness of many ligands (PMC).

Other names

T2R4T2R14TRB1Taste 2 receptor member 4Taste 2 receptor member 14Bitter taste receptor 4Bitter taste receptor 14

Agonism of TAS2R4 and TAS2R14 activates G protein-mediated signaling (typically via gustducin or Gαi/o), leading to the activation of phospholipase C beta 2 (PLCβ2) and the subsequent release of intracellular calcium (UniProt, PMC). In airway smooth muscle, this increase in calcium leads to bronchodilation, likely through the activation of large-conductance calcium-activated potassium (BKCa) channels or the inhibition of L-type voltage-gated calcium channels (PubMed, 2022). In cancer cells, TAS2R activation modulates pathways such as MAPK/ERK and RhoGTPase to inhibit cell migration and proliferation (PMC, 2024).